Differences in genomic abnormalities among African individuals with monoclonal gammopathies using calculated ancestry

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Multiple myeloma (MM) is two- to three-fold more common in African Americans (AAs) compared to European Americans (EAs). This striking disparity, one of the highest of any cancer, may be due to underlying genetic predisposition between these groups. There are multiple unique cytogenetic subtypes of MM, and it is likely that the disparity is associated with only certain subtypes. Previous efforts to understand this disparity have relied on self-reported race rather than genetic ancestry, which may result in bias. To mitigate these difficulties, we studied 881 patients with monoclonal gammopathies who had undergone uniform testing to identify primary cytogenetic abnormalities. DNA from bone marrow samples was genotyped on the Precision Medicine Research Array and biogeographical ancestry was quantitatively assessed using the Geographic Population Structure Origins tool. The probability of having one of three specific subtypes, namely t(11;14), t(14;16), or t(14;20) was significantly higher in the 120 individuals with highest African ancestry (≥80%) compared with the 235 individuals with lowest African ancestry (<0.1%) (51% vs. 33%, respectively, p value = 0.008). Using quantitatively measured African ancestry, we demonstrate a major proportion of the racial disparity in MM is driven by disparity in the occurrence of the t(11;14), t(14;16), and t(14;20) types of MM.

Original languageEnglish (US)
Article number96
JournalBlood Cancer Journal
Volume8
Issue number10
DOIs
StatePublished - Oct 1 2018

Fingerprint

Paraproteinemias
Multiple Myeloma
Precision Medicine
Genetic Predisposition to Disease
Cytogenetics
Chromosome Aberrations
African Americans
Bone Marrow
DNA
Research
Population
Neoplasms

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

@article{756b43f2e54e4560a63b6caf6a80d455,
title = "Differences in genomic abnormalities among African individuals with monoclonal gammopathies using calculated ancestry",
abstract = "Multiple myeloma (MM) is two- to three-fold more common in African Americans (AAs) compared to European Americans (EAs). This striking disparity, one of the highest of any cancer, may be due to underlying genetic predisposition between these groups. There are multiple unique cytogenetic subtypes of MM, and it is likely that the disparity is associated with only certain subtypes. Previous efforts to understand this disparity have relied on self-reported race rather than genetic ancestry, which may result in bias. To mitigate these difficulties, we studied 881 patients with monoclonal gammopathies who had undergone uniform testing to identify primary cytogenetic abnormalities. DNA from bone marrow samples was genotyped on the Precision Medicine Research Array and biogeographical ancestry was quantitatively assessed using the Geographic Population Structure Origins tool. The probability of having one of three specific subtypes, namely t(11;14), t(14;16), or t(14;20) was significantly higher in the 120 individuals with highest African ancestry (≥80{\%}) compared with the 235 individuals with lowest African ancestry (<0.1{\%}) (51{\%} vs. 33{\%}, respectively, p value = 0.008). Using quantitatively measured African ancestry, we demonstrate a major proportion of the racial disparity in MM is driven by disparity in the occurrence of the t(11;14), t(14;16), and t(14;20) types of MM.",
author = "Linda Baughn and Kathryn Pearce and Dirk Larson and Mei-Yin Polley and Eran Elhaik and Michael Baird and Colin Colby and Joanne Benson and Zhuo Li and Yan Asmann and Therneau, {Terry M} and Cerhan, {James R} and Vachon, {Celine M} and Stewart, {Alexander Keith} and Bergsagel, {Peter Leif} and Angela Dispenzieri and Kumar, {Shaji K} and Rajkumar, {S Vincent}",
year = "2018",
month = "10",
day = "1",
doi = "10.1038/s41408-018-0132-1",
language = "English (US)",
volume = "8",
journal = "Blood Cancer Journal",
issn = "2044-5385",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Differences in genomic abnormalities among African individuals with monoclonal gammopathies using calculated ancestry

AU - Baughn, Linda

AU - Pearce, Kathryn

AU - Larson, Dirk

AU - Polley, Mei-Yin

AU - Elhaik, Eran

AU - Baird, Michael

AU - Colby, Colin

AU - Benson, Joanne

AU - Li, Zhuo

AU - Asmann, Yan

AU - Therneau, Terry M

AU - Cerhan, James R

AU - Vachon, Celine M

AU - Stewart, Alexander Keith

AU - Bergsagel, Peter Leif

AU - Dispenzieri, Angela

AU - Kumar, Shaji K

AU - Rajkumar, S Vincent

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Multiple myeloma (MM) is two- to three-fold more common in African Americans (AAs) compared to European Americans (EAs). This striking disparity, one of the highest of any cancer, may be due to underlying genetic predisposition between these groups. There are multiple unique cytogenetic subtypes of MM, and it is likely that the disparity is associated with only certain subtypes. Previous efforts to understand this disparity have relied on self-reported race rather than genetic ancestry, which may result in bias. To mitigate these difficulties, we studied 881 patients with monoclonal gammopathies who had undergone uniform testing to identify primary cytogenetic abnormalities. DNA from bone marrow samples was genotyped on the Precision Medicine Research Array and biogeographical ancestry was quantitatively assessed using the Geographic Population Structure Origins tool. The probability of having one of three specific subtypes, namely t(11;14), t(14;16), or t(14;20) was significantly higher in the 120 individuals with highest African ancestry (≥80%) compared with the 235 individuals with lowest African ancestry (<0.1%) (51% vs. 33%, respectively, p value = 0.008). Using quantitatively measured African ancestry, we demonstrate a major proportion of the racial disparity in MM is driven by disparity in the occurrence of the t(11;14), t(14;16), and t(14;20) types of MM.

AB - Multiple myeloma (MM) is two- to three-fold more common in African Americans (AAs) compared to European Americans (EAs). This striking disparity, one of the highest of any cancer, may be due to underlying genetic predisposition between these groups. There are multiple unique cytogenetic subtypes of MM, and it is likely that the disparity is associated with only certain subtypes. Previous efforts to understand this disparity have relied on self-reported race rather than genetic ancestry, which may result in bias. To mitigate these difficulties, we studied 881 patients with monoclonal gammopathies who had undergone uniform testing to identify primary cytogenetic abnormalities. DNA from bone marrow samples was genotyped on the Precision Medicine Research Array and biogeographical ancestry was quantitatively assessed using the Geographic Population Structure Origins tool. The probability of having one of three specific subtypes, namely t(11;14), t(14;16), or t(14;20) was significantly higher in the 120 individuals with highest African ancestry (≥80%) compared with the 235 individuals with lowest African ancestry (<0.1%) (51% vs. 33%, respectively, p value = 0.008). Using quantitatively measured African ancestry, we demonstrate a major proportion of the racial disparity in MM is driven by disparity in the occurrence of the t(11;14), t(14;16), and t(14;20) types of MM.

UR - http://www.scopus.com/inward/record.url?scp=85054626458&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054626458&partnerID=8YFLogxK

U2 - 10.1038/s41408-018-0132-1

DO - 10.1038/s41408-018-0132-1

M3 - Article

VL - 8

JO - Blood Cancer Journal

JF - Blood Cancer Journal

SN - 2044-5385

IS - 10

M1 - 96

ER -